1.
The Research Progress of Host Genes and Tuberculosis Susceptibility.
Cai, L, Li, Z, Guan, X, Cai, K, Wang, L, Liu, J, Tong, Y
Oxidative medicine and cellular longevity. 2019;:9273056
Abstract
BACKGROUND/AIMS: Nucleotide diversity may affect the immune regulation of tuberculosis (TB) patients, leading to the individual susceptibility to TB. In recent years, there are a lot of researches on the association of host genetic factors and TB susceptibility which has attracted increasing attention, and the in-depth study of its mechanism is gradually clear. MATERIALS We made a minireview on the association of many candidate genes with TB based on recent research studies systematically, such as the human leukocyte antigen (HLA) gene, the solute carrier family 11 member 1 (SLC11A1) gene system, the vitamin D receptor (VDR) gene, the mannan-binding lectin (MBL) gene, the nitric oxide synthase 2A (NOS2A) gene, the speckled 110 (SP110) gene, and the P2X7 receptor (P2X7) gene. The discovery of these candidate genes could reveal the pathogenesis of TB comprehensively and is crucial to provide scientific evidence for formulating the related measures of prevention and cure. DISCUSSION The host genes play important roles in the development of TB, and the host genes may become new targets for the prevention and treatment of TB. Effective regulation of host genes may help prevent or even treat TB. CONCLUSION This minireview focuses on the association of host genes with the development of TB, which may supply some clues for future therapies and novel drug targets for TB.
2.
Genetically-determined hyperfunction of the S100B/RAGE axis is a risk factor for aspergillosis in stem cell transplant recipients.
Cunha, C, Giovannini, G, Pierini, A, Bell, AS, Sorci, G, Riuzzi, F, Donato, R, Rodrigues, F, Velardi, A, Aversa, F, et al
PloS one. 2011;(11):e27962
Abstract
Invasive aspergillosis (IA) is a major threat to the successful outcome of hematopoietic stem cell transplantation (HSCT), although individual risk varies considerably. Recent evidence has established a pivotal role for a danger sensing mechanism implicating the S100B/receptor for advanced glycation end products (RAGE) axis in antifungal immunity. The association of selected genetic variants in the S100B/RAGE axis with susceptibility to IA was investigated in 223 consecutive patients undergoing HSCT. Furthermore, studies addressing the functional consequences of these variants were performed. Susceptibility to IA was significantly associated with two distinct polymorphisms in RAGE (-374T/A) and S100B (+427C/T) genes, the relative contribution of each depended on their presence in both transplantation counterparts [patient SNP(RAGE), adjusted hazard ratio (HR), 1.97; P = 0.042 and donor SNP(RAGE), HR, 2.03; P = 0.047] or in donors (SNP(S100B), HR, 3.15; P = 7.8e-(4)) only, respectively. Functional assays demonstrated a gain-of-function phenotype of both variants, as shown by the enhanced expression of inflammatory cytokines in RAGE polymorphic cells and increased S100B secretion in vitro and in vivo in the presence of the S100B polymorphism. These findings point to a relevant role of the danger sensing signaling in human antifungal immunity and highlight a possible contribution of a genetically-determined hyperfunction of the S100B/RAGE axis to susceptibility to IA in the HSCT setting.
3.
Genetic polymorphisms in vitamin D receptor, vitamin D-binding protein, Toll-like receptor 2, nitric oxide synthase 2, and interferon-gamma genes and its association with susceptibility to tuberculosis.
Leandro, AC, Rocha, MA, Cardoso, CS, Bonecini-Almeida, MG
Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas. 2009;(4):312-22
Abstract
Mycobacterium tuberculosis kills more people than any other single pathogen, with an estimated one-third of the world's population being infected. Among those infected, only 10% will develop the disease. There are several demonstrations that susceptibility to tuberculosis is linked to host genetic factors in twins, family and associated-based case control studies. In the past years, there has been dramatic improvement in our understanding of the role of innate and adaptive immunity in the human host defense to tuberculosis. To date, attention has been paid to the role of genetic host and parasitic factors in tuberculosis pathogenesis mainly regarding innate and adaptive immune responses and their complex interactions. Many studies have focused on the candidate genes for tuberculosis susceptibility ranging from those expressed in several cells from the innate or adaptive immune system such as Toll-like receptors, cytokines (TNF-alpha, TGF-beta, IFN-gamma, IL-1b, IL-1RA, IL-12, IL-10), nitric oxide synthase and vitamin D, both nuclear receptors and their carrier, the vitamin D-binding protein (VDBP). The identification of possible genes that can promote resistance or susceptibility to tuberculosis could be the first step to understanding disease pathogenesis and can help to identify new tools for treatment and vaccine development. Thus, in this mini-review, we summarize the current state of investigation on some of the genetic determinants, such as the candidate polymorphisms of vitamin D, VDBP, Toll-like receptor, nitric oxide synthase 2 and interferon-gamma genes, to generate resistance or susceptibility to M. tuberculosis infection.